Pediatric Immunologists Research Articles

Allergen-specific immunotherapy in children. Consensus document of the Association of Pediatric Allergologists and Immunologists of Russia (positional pаper)

The Document contains fundamental provisions regarding allergen specific immunotherapy in children.International clinical recommendations on the methodology were used, adapted for use in real practice.In the absence of international recommendations, the authors present the consensus opinion of the project participants, based on data from clinical studies in this area.At the moment, we bring to your attention a position paper on allergen specific immunotherapy in children, created by experts from the Association of Pediatric Allergologists and Immunologists of Russia (APAIR) based on the 2021 consensus document, with the necessary data updates.

Chronic neutropenia in childhood: experience of a tertiary center

ObjectiveTo assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. MethodsRetrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. ResultsA total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. ConclusionAIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

Intractable diarrhea in infancy and molecular analysis: We are beyond the tip of the iceberg

BackgroundIntractable diarrhea (ID) could be defined as a syndrome of severe chronic diarrhea associated with malnutrition not easily resolved by conventional management. AimsTo provide an overview on etiology and management of ID patients in Italy in the last 12 years. MethodsThe members of Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) enrolled all ID patients seen between January 1, 2011 and December 31, 2022. Results69 children were enrolled (49 M, 20 F; median age at ID onset 9.5 days) from 7 tertiary care pediatric centers. Overall 62 patients had genetic diseases; 3 had infantile Inflammatory Bowel Disease and 1 autoimmune enteropathy in absence of genetic mutations; 2 undefined ID. Defects of intestinal immune-related homeostasis caused ID in 29 patients (42 %). ConclusionID is a rare but challenging problem, although the potential for diagnosis has improved over time. In particular, molecular analysis allowed to identity genetic defects in 90 % of patients and to detect new genetic mutations responsible for ID. Due to both the challenging diagnosis and the treatment for many of these diseases, the close relationship between immune system and digestive tract should require a close collaboration between pediatric immunologists and gastroenterologists, to optimize epidemiologic surveillance and management of ID.

Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD. Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded. Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children aged under 2 years and 9 for those 2 years and over. This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

Déficits immunitaires combinés sévères : de la clinique aux explorations immunologique et génétique

AbstractAmong primary immunodeficiencies, severe combined immunodeficiency disorders are revealed by any type of severe infection, or inflammatory skin lesions, which occur early in life. Here, will be expose their clinical and genetic characteristics that need to be known to allow detection and to avoid a systematic lethal evolution without proper treatment. We emphasize that any white blood cells count showing a lymphopenia under 3500/mm3 during the first year of life needs to be explored in emergency with a pediatric immunologist.

Outcomes and impact of multidisciplinary team care on immunologic and hemato-oncologic pediatric patients.

Immunologic and hemato-oncologic disorders in the pediatric population represent an interrelated and complex group of conditions whose approach, diagnosis, and management could be difficult. Multidisciplinary teams have been proved beneficial in treating such complexities. We conducted a retrospective observational study at a tertiary hospital in Madrid, Spain, which is a pediatric immunology and onco-hematology referral center. We included all patients of multidisciplinary outpatient consultation, comprising a working group of pediatric oncohematologists and immunologists, between April 2016 and December 2019. Epidemiologic, clinical, and laboratory data were collected. We analyzed these data and established a relationship between age and findings of final diagnosis as well as variance on diagnoses prior to their multidisciplinary assessment and number of visits to the consultation. In all, 93 children and adolescents were included in this study. Laboratory abnormalities were the most frequent reason for being referred to our unit (87.2%); 78% of children had a previously diagnosed comorbidity. Before starting follow-up in the multidisciplinary consultation, 14% of patients were diagnosed, and after the study by the multidisciplinary team, the final diagnosis was reached in 58.1% of patients. No correlation was discovered between final diagnosis and gender (P = 0.29), age (biserial correlation coefficient, r = 0.036, P = 0.70), and number of visits (P = 0.07). A multidisciplinary approach to immunologic, hematologic, and oncologic pediatric diseases is feasible. It can be a powerful and useful tool for diagnosis and treatment, especially in complex pediatric patients.

654: TIMING OF MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN IN RELATION TO INDEX COVID-19 INFECTION

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) Results from Immune Dysregulation Following COVID-19 Infection. Timing of MIS-C Diagnosis in Relation to Index COVID-19 Infection Varies. The CDC Reports the Average Time Between MIS-C and COVID-19 Infection is 4 Weeks. We Aim to Determine if the Timing of MIS-C Diagnosis in Relation to the Index COVID-19 Infection Varies by Variant, and Whether Spike IgG Value Correlates with the Time Between COVID-19 and MIS-C or with Peak Ferritin. Methods: Our MIS-C Team (Pediatric Cardiologists, Rheumatologists, Immunologists, Hematologists, Intensivists, and Hospitalists) Reviewed Every Suspected Case of MIS-C at our Institution, and All Confirmed Cases Were Reported to the State Health Department. Electronic Health Records Were Reviewed to Obtain Data Elements in this IRB Exempt Study. COVID-19 Variant Timeframes Were Defined by Dominant (>50% cases) Strand in the United States (Alpha/Beta/Gamma 1/21/20-6/25/21, Delta 6/26/21-12/17/21, and Omicron 12/18/21-Present). Results: Our MIS-C Team Identified 68 Cases from 7/2/20 to 6/22/22 out of 226 (30%) Confirmed in South Carolina. We Categorized Each Case by COVID-19 Definition (Exposure, Positive Test, or Unknown). The COVID-19 Component of the Definition was Based on Exposures in 25 (37%), 25 (37%) Positive Antigen Test or PCR, and 18 (26%) Positive IgG. Mean Time Between COVID Exposure or Positive Test and MIS-C Diagnosis was 31.5d. Mean Time for Alpha/Beta/Gamma Variant was 27.3d, Delta 33.6d, and Omicron 34.2d. 100% of Cases Received IVIG, 72% IVIG and Steroids, and 13% IVIG, Steroids, and Anakinra. Relationship Between Spike IgG and Timeframe of MIS-C (r=0.61), Peak Ferritin and Anakinra (r=0.63), and Peak Ferritin and Timeframe of MIS-C (r=0.34). Only 4% of Those Vaccine-Eligible at the Time of Illness Were Fully Vaccinated. Conclusions: The Timing of MIS-C Diagnosis in Relation to the Index of COVID-19 Infection does Vary by Variant with a 6.9 Day Increase in Average Since the Start of the Pandemic. Our Overall Average of 31.5 Days (4.5 Weeks) Between COVID-19 and MIS-C Supports the Initial CDC Estimate of 4 Weeks. There was a Moderate Positive Correlation Between Spike IgG and Timeframe of MIS-C, and a Higher Peak Ferritin Indicated use of Anakinra.

Practice Variations in the Management of Infants With Non-IgE-Mediated Cow's Milk Protein Allergy.

Infants with non-IgE-mediated food allergies are often referred to gastroenterologists or immunologists. We hypothesized that there are practice variations between these disciplines in the diagnosis and management of such infants. A computerized questionnaire was distributed between pediatric gastroenterologists and immunologists. The questions addressed diagnosis, management, and follow-up in 3 scenarios of infants with concern for food protein-induced allergic proctocolitis (FPIAP) due to non-IgE-mediated responses to cow's milk. Three cases of infants with suspected FPIAP were presented: milk-based formula-fed (case 1) or breast-fed (case 2) infants that are well appearing and thriving, and a breast-fed infant who is not growing appropriately along with a personal and family history of atopy (case 3). Fifty-eight pediatric gastroenterologists and 32 immunologists completed the questionnaire. Significant differences between gastroenterologists and immunologists were noted regarding the recommended dietary changes in these scenarios. Moreover, despite available guidelines generated by both societies, most physicians confirm the diagnosis based on resolution of symptoms after the dietary change, without re-exposure to the the suspected trigger. In addition, time for recommended re-exposure in infants with FPIAP was also different; most gastroenterologists recommended waiting until 12 months of age, while immunologists suggested reintroduction earlier, up to 6 months of age. We identified significant practice variations in diagnosis and management of FPIAP between pediatric gastroenterologists and immunologists, with lack of adherence to society guidelines. Joint task forces of primary care pediatricians, gastroenterologists, and immunologists should provide uniform guidelines to standardize care.

Clinical and immunological assessment of APDS2 with features of the SHORT syndrome related to a novel mutation in PIK3R1 with reduced penetrance.

Monoallelic loss-of-function (LOF) mutations in the phosphatidylinositol 3-kinase (PIK3R1) gene affecting the inter-Src homology 2 domain of the p85α regulatory subunit of phosphoinositide--3-kinase δ (PI3Kδ) cause the activated PI3K δ syndrome (APDS2). APDS2 is defined as a primary antibody deficiency, developmental abnormalities within the B and T lymph cell compartments, and immune dysregulation. The genetic defect of APDS2 is shared with that of the SHORT syndrome, characterized by short stature, joint hyperextensibility, ocular depression, Rieger anomaly, and delayed tooth eruption. LOF variants in an intronic splice site (c.1425+1G.C/A/T) in the PI3KR1 gene have been identified in patients affected with both APDS2 and SHORT syndrome. Herein, we report a novel c.1644-1648del (p.Asp548Glufs*6) variant in a pediatric patient with the APDS2-related immunodeficiency, who presents with mild phenotypic features of the SHORT syndrome, congenital chest wall deformity, and IgE-mediated food allergy. The same variant was also identified in the patient's hitherto asymptomatic mother, implicating an incomplete penetrance. Regular monitoring by a multidisciplinary team under the pediatric clinical immunologist's supervision to implement appropriate diagnostic procedures and treatment modalities is of paramount importance. Further studies are required to better define the genotype-phenotype correlation in patients with the PIK3R1 gene mutations and to better delineate the mutual relationship between APDS2 and the SHORT syndrome.

The Relationship Between Serum Level of Interleukin-33 and Allergic Rhinitis and Its Severity in Children

Background: T helper type 2 (Th2) cells are critical cellular elements in allergic rhinitis. Interleukin-33 (IL-33) produces Th2-related cytokines and binds to the ST2 receptors. This is expressed strongly in mastocytes and discerningly in Th2 cells. Through Th2 cells, IL-33 may also have partly involved in immune responses. Objectives: This study aimed to measure the IL-33 serum levels in children suffering from allergic rhinitis and investigate its relationship with the disease. Methods: This case-control study was conducted on a population with the age range of 7-18 years, who referred to the Pediatric Clinic of the Shahid Beheshti Hospital in Kashan, Iran, in 2017. The study sample encompassed 57 patients with allergic rhinitis (case group) and 57 subjects with no allergic rhinitis (control group). The ELISA assay was used to measure the serum level of IL-33 in the case and control groups. Allergic rhinitis was diagnosed by a pediatric immunologist considering the patient’s history and the guidelines set out by the Allergic Rhinitis and its Impact on Asthma (ARIA). All study data were analyzed with SPSS software version 22. Results: There were significant differences between the two groups in terms of age (P = 0.001), gender (P = 0.0144), family history of atopy (P < 0.001), symptoms duration (P < 0.001), and comorbidities (e.g., atopic dermatitis and asthma) (P < 0.001). Furthermore, compared to the control group, the case group exhibited significantly higher IL-33 serum levels (P < 0.001). Conclusions: The high serum levels of IL-33 exhibited in patients with allergic rhinitis indicate its involvement in the pathogenesis of the concerned disease.

Unnecessary Referrals to Pediatric Immunology Services.

Immunology is highly specialized and utilized in prophylactic vaccines, laboratory tests and treatments for patient care. It is also an essential tool for cutting-edge biomedical research designed to deepen scientific understanding and produce new therapies and technologies.[1] At the William Soler Pediatric University Hospital in Havana, as pediatric immunologists, we work to improve our patients’ […]

Of Blindness, Elephants, and Multidisciplinary Collaboration.

Of Blindness, Elephants, and Multidisciplinary Collaboration.

Створення онлайн-тесту для виявлення в дітей підозри на вроджені помилки імунітету

As of 2020, more than 400 nosologies of primary immunodeficiencies are known. For most children with this pathology, the key immunological diagnosis remains unclear due to the lack of pathognomonic symptoms, as well as low medical alertness due to the relative rarity of these diseases. Primary immunodeficiencies are not fatal if diagnosed early, moreover, they are treatable with the possibility of a full life or complete recovery. Today, information technology has become an integral part of everyday life. The ability to evaluate a clinical patient record online is a modern important step. Purpose — to create an online test, available to both physicians and patients, to detect suspicious cases of primary immunodeficiencies in children based on possible clinical manifestations. Material and methods. Collection and analysis of a child's clinical record on suspicious manifestations of primary immunodeficiency, age and gender comparisons using web technologies. (PHP, MySQL). Results. International and Ukrainian developments of clinical criteria for suspected primary immunodeficiency in a child have been transformed into an online test containing 35 clinical inquiries to a child's parents or attending physician, followed by analysis of a child's gender and age. As a result, the test user receives the result of the alertness level in terms of urgency to consult a pediatric immunologist. Conclusions. The immunological online test showed considerable interest, a high detection rate of suspicious cases of primary immunodeficiency. The test can be used with patients who come for an appointment or with hospital patients. The study was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution specified in the work. Informed consent was obtained from the parents of the children for the research. The authors declare no conflicts of interest. Key words: pediatric immunology, primary immunodeficiencies, online, test, clinical criteria.

Managing Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders: e-GLILDnet International Clinicians Survey.

BackgroundGranulomatous–lymphocytic interstitial lung disease (GLILD) is a rare, potentially severe pulmonary complication of common variable immunodeficiency disorders (CVID). Informative clinical trials and consensus on management are lacking.AimsThe European GLILD network (e-GLILDnet) aims to describe how GLILD is currently managed in clinical practice and to determine the main uncertainties and unmet needs regarding diagnosis, treatment and follow-up.MethodsThe e-GLILDnet collaborators developed and conducted an online survey facilitated by the European Society for Immunodeficiencies (ESID) and the European Respiratory Society (ERS) between February–April 2020. Results were analyzed using SPSS.ResultsOne hundred and sixty-one responses from adult and pediatric pulmonologists and immunologists from 47 countries were analyzed. Respondents treated a median of 27 (interquartile range, IQR 82–maximum 500) CVID patients, of which a median of 5 (IQR 8–max 200) had GLILD. Most respondents experienced difficulties in establishing the diagnosis of GLILD and only 31 (19%) had access to a standardized protocol. There was little uniformity in diagnostic or therapeutic interventions. Fewer than 40% of respondents saw a definite need for biopsy in all cases or performed bronchoalveolar lavage for diagnostics. Sixty-six percent used glucocorticosteroids for remission-induction and 47% for maintenance therapy; azathioprine, rituximab and mycophenolate mofetil were the most frequently prescribed steroid-sparing agents. Pulmonary function tests were the preferred modality for monitoring patients during follow-up.ConclusionsThese data demonstrate an urgent need for clinical studies to provide more evidence for an international consensus regarding management of GLILD. These studies will need to address optimal procedures for definite diagnosis and a better understanding of the pathogenesis of GLILD in order to provide individualized treatment options. Non-availability of well-established standardized protocols risks endangering patients.

Newborn Screening for Severe Combined Immunodeficiency and T–Cell Lymphopenia in California, 2010–2017

To evaluate the diagnostic capability of the T-cell receptor excision circles– (TRECs) based newborn screen (NBS) for severe combined immunodeficiency disease (SCID) in California.The population studied includes all infants born in hospitals in California from 2010 to 2016, with the exception of families opting out for religion.Dried blood spot specimens were obtained from the infants via heel punch for DNA extraction and evaluation of TREC count as a part of the NBS. TREC testing was initially performed at a single facility in California until 2015 and then in regional laboratories across the state starting in 2015, using a new neonatal TREC kit. Threshold values for positive screening results were therefore adjusted after the change of methods. Infants with positive screen results or 2 indeterminate screen results obtained laboratory testing for complete blood count and lymphocyte subsets. Infants with <300 absolute T cells per microliter were referred to SCID medical centers, and those with up to 1500 T cells per microliter were managed by pediatric immunologists. All patients continued to be monitored by their general practitioners for the next 6.5 years.A total of 3 252 156 infants underwent SCID newborn screening from August 2010 to March 2017. A total of 562 infants had abnormal screen results, and 213 infants (1 in 15 300 [95% CI: 1 per 13 500 to 1 per 17 700]) were confirmed to have T-cell lymphopenia (TCL) (<1500 cells per microliter). Fifty cases of SCID (1 per 65 000 births [95% CI: 1 per 51 000 to 1 per 90 000]) were identified with TREC screening. The remaining 162 cases of TCL were due to congenital abnormalities, other primary immunodeficiencies, self-limiting TCL, or idiopathic TCL. Infants who were premature or small for gestational age were more likely to demonstrate positive or indeterminate TREC screening results and subsequently noted to have TCL. Forty-nine of 50 children identified with SCID were referred to centers for further management, with 47 children presenting to medical care before any infectious complication (2 developed infection and rash). Forty-six infants (94%) with SCID received a bone marrow transplant, gene therapy, or enzyme replacement therapy and survived. Two of the 50 SCID patients had delayed diagnosis after toddlerhood and were not identified by the TREC screening. Urgent positive test results requiring immediate call back for lymphocyte screen (<4 TRECs) identified 90% of infants with SCID.TREC screening in California has proven to be highly sensitive and specific in the identification of SCID in newborn infants. The test allows infants with SCID and other TCLs to be identified in a timely manner, allowing for early intervention and treatment of these infants.The study demonstrates that identification of patients with TCL is accurate and shows the benefits of early detection of patients who are likely to have SCID. Early management has led to high survival rates posttreatment, likely because most interventions occurred before serious infection. Similar incidences of disease and outcomes were seen in the first 2 years of TREC NBS in California, (J Allergy Clin Immunol. 2013;132[1]:140–150), thus supporting the long-term reliability of TREC testing and its addition to the NBS panel.

Guidance for assessment of erythroderma in neonates and infants for the pediatric immunologist.

Neonatal and infantile erythroderma (NIE) represents the common clinical phenotype of heterogeneous diseases ranging from benign and transient skin conditions to fatal multiorgan disorders. NIE regularly demands a comprehensive diagnostic workup in a multiprofessional setting, especially if newborns and young infants with the disease develop a failure to thrive and concomitant infectious, neurologic, or metabolic complications. By obtaining a detailed medical history and performing a thorough clinical examination, targeted diagnostic steps can be scheduled for most affected children. If NIE occurs in the early neonatal period, lesional skin biopsy and histology are often indicated. Likewise, if monogenic skin or immunologic diseases are suspected, genetic testing with customized panels of potentially underlying genes is mandatory. Of note, if acute symptoms such as severe infections, metabolic acidosis, or seizures occur, rapid microbiologic and metabolic investigations are warranted to rule out immunodeficiency and inborn errors of metabolism.

Antihistamines in pediatric allergology

Allergic diseases without a doubt have become one of the biggest problems of pediatrics in recent decades. One of the evidence of this is the maximum occupancy of halls at the IV All-Russian Congress of the Association of Pediatric Allergists and Immunologists of Russia. The symposium «Antihistamines in children’s allergology» was among the most popular.

Killer Infection: Is It Your Genes?

The article focuses on research into the genetics of bacterial and viral disease susceptibility. It states that susceptibility to specific infection types such as Candida can run in families. It mentions geneticist and pediatric immunologist Jean-Laurent Casanova and colleagues identified two gene defects that limit the production of virus-fighting interferons that causes influenza susceptibility, while a category of mutation increases the risk of infection to herpes simplex encephalitis.

Contribution of the use of basic telemedicine tools to the care of children and adolescents with juvenile idiopathic arthritis at the Puerto Montt Hospital, Chile.

Reporting 10 years of experience of a mixed care model: face-to-face and distance, using basic TM; the institutional impact, advantages, disadvantages and acceptance informed by parents and patients. Exploratory, descriptive, and re trospective study with qualitative component. After the authorization of a scientific-ethics committee of the Reloncaví Health Service and the application of informed consent, a review of medical records was carried out and a qualitative survey was applied to parents and children over 14 years of age with JIA, seen between 2005-2015 in the pediatric ambulatory rheumatology polyclinic of Puerto Montt Hospital. The were 27/35 participating patients with JIA attended by a trained pediatrician and assisted by distance (1,000 km) by an immunologist. The 8/35 patients did not answer by choice or change of address. The 70% of parents and patients accepted the model of care and 4% would pre fer sporadic care only by specialists for diagnosis and follow-up. The number of patients transferred annually decreased from 10 to 1. The advantages of the care model outweighed the disadvantages perceived by parents and JIA patients. The use of TM tools in JIA decreased transfers, improved follow-up and were considered advantageous by patients and their parents.

Inflammatory bowel disease in chronic granulomatous disease: An emerging problem over a twenty years' experience.

Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocytes, characterized by life-threatening infections and hyperinflammation. Due to survival improvement, inflammatory bowel disease (IBD) is becoming increasingly relevant. Here, we report our 20year experience. We retrospectively analyzed clinic, endoscopic, and histologic features, as well as the management of CGD-IBD patients referred to the Bambino Gesù Children's Hospital in Rome, Italy. Of 20 patients with CGD, 9 presented with CGD-IBD at diagnosis and/or during follow-up. Symptoms occurred at a median age of 16years (range 3.2-42), with a median delay of 6months for endoscopic confirmation. Patients mainly complained of nonspecific diarrhea (55%), with discrepancy between symptom paucity and severe endoscopic appearance, mainly represented by extensive colonic involvement (44%). Histology revealed at least 2 characteristic features (epithelioid granulomas, pigmented macrophages, and increased eosinophils) in 78% of patients. Eight of 9 patients received oral mesalamine, and 5 required systemic steroids. One patient received azathioprine due to steroid dependence. No patient required biological therapy or surgery. Clinical remission was obtained in all patients, but the majority complained of mild relapses. Two episodes of severe infection occurred early after steroid therapy. Penetrance of CGD-IBD increases with age. Clinical manifestations may be subtle, and clinicians should have a low threshold to recommend endoscopy. Treatment with NSAIDs and/or steroids achieves a good response, but relapses usually occur. Infection surveillance is mandatory during treatment, to prevent opportunistic infections. A close collaboration between pediatric immunologists and gastroenterologists is pivotal, including combined follow-up.